The two objectives of the Human Cancer Serology Program are: I. Serological definition and biochemical characterization of distinctive cell surface antigens of human cancer and II. immunovirologic analysis and biochemical characterization of human cancers of suspected viral etiology. The proposed studies relate to two central questions concerning human cancer: Do human tumor-specific antigens exist and do viruses play a role in the etiology of human cancer? The technique of autologous typing of malignant cells will be used to analyze cell surface antigens of malignant melanoma, renal cancer, astrocytoma, leukemia, lymphoma, and ovarian cancer, and will be applied to breast, lung, and colon cancer as improved methods for the in vitro propagation of these cancers are developed. Serological definition of tumor-specific cell surface antigens of human cancer will be followed by: a) Genetic analysis to determine the chromosomal loci specifying these antigens, b) search for natural antibody to these antigens in the normal human population, c) biochemical characterization, d) assessment of the clinical significance of humoral immunity to these antigens in patients with cancer, and e) development of maximally immunogenic forms of cancer vaccines. Immunovirological studies will focus on selected human cancers that are suspected from serological, virological, and epidemiological evidence to be related to herpesviruses or papovaviruses. The following associations will be investigated: The relation of cytomegalovirus to Kaposi's sarcoma, genital cancer, and colon cancer; the relation of Epstein-Barr virus to nasopharyngeal cancer, and the relation of BK and JC papovaviruses to brain cancer, renal cancer, and cancers developing in immunodeficient patients. Using a variety of serological assays and reference viral antigens and antibodies to identify the range of herpesvirus and papovavirus antigens, evidence will be sought for the presence of viral antigens in human cancer cells and for the occurrence of corresponding antibody in patients with cancer as compared with the normal population.